Various wild mice are resistant to induction of erythroblastosis by Friend complex virus. The Japanese mouse, M. m. molossinus, carries a locus apparently identical to the Friend virus resistance gene, Fv-4, described originally in G strain mice. Sensitivity to Friend complex disease was examined in these mice to characterize Fv-4, and identify any other genetic factors which influence virus replication and the development of disease. Southern blot hybridization has shown that a novel ecotropic envelope-related sequence is integrated at or near the Fv-4 locus. Infectious ecotropic virus cannot be induced from mice carrying only Fv-4 associated sequences, but immunological methods have identified a unique cell surface antigen on the thymocytes of Fv-4 resistant mice which shows the serological reactivity of an ecotropic envelope glycoprotein. The restriction map of this sequence is different from that of other ecotropic proviruses, and this sequence is now being molecularly cloned for further analysis. A number of other feral mice are also resistant to Friend complex disease, and several of these mice also carry this Fv-4 associated sequence. However, the resistance shown by M. spretus more closely resembles that shown by Fv-2 resistant mice, and results of crosses with Fv-2 sensitive and resistant inbred mice suggest that M. spretus carries the resistance allele at this locus.